methyl {(2R,4S)-1-[(1R)-4,4-dimethyl-1-(3,3,3-trifluoropropyl)pentyl]-3,3-difluoro-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate | 1011481-24-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: methyl {(2R,4S)-1-[(1R)-4,4-dimethyl-1-(3,3,3-trifluoropropyl)pentyl]-3,3-difluoro-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate
• 英文别名: methyl 2-[(2R,4S)-3,3-difluoro-1-[(4R)-1,1,1-trifluoro-7,7-dimethyloctan-4-yl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl]acetate
• CAS: 1011481-24-5
• 化学式: C₂₅H₃₃F₈NO₂
• 分子量: 531.53
• InChiKey: FBYQOYPEYDYWKM-QKNQBKEWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  methyl {(2R,4S)-1-[(1R)-4,4-dimethyl-1-(3,3,3-trifluoropropyl)pentyl]-3,3-difluoro-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 {(2R,4S)-1-[(1R)-4,4-dimethyl-1-(3,3,3-trifluoropropyl)pentyl]-3,3-difluoro-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetic acid
  参考文献：
  名称：

  Fluorinated piperidine acetic acids as γ-secretase modulators

  摘要：

  We report herein a novel series of difluoropiperidine acetic acids as modulators of gamma-secretase. Synthesis of 2-aryl-3,3-difluoropiperidine analogs was facilitated by a unique and selective beta-difluorination with Selectfluor (R). Compounds 1f and 2c were selected for in vivo assessment and demonstrated selective lowering of A beta 42 in a genetically engineered mouse model of APP processing. Moreover, in a 7-day safety study, rats treated orally with compound 1f (250 mg/kg per day, AUC(0-24) = 2100 mu M h) did not exhibit Notch-related effects. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.034
• 作为产物：
  描述：

  在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 生成 methyl {(2R,4S)-1-[(1R)-4,4-dimethyl-1-(3,3,3-trifluoropropyl)pentyl]-3,3-difluoro-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate
  参考文献：
  名称：

  Fluorinated piperidine acetic acids as γ-secretase modulators

  摘要：

  We report herein a novel series of difluoropiperidine acetic acids as modulators of gamma-secretase. Synthesis of 2-aryl-3,3-difluoropiperidine analogs was facilitated by a unique and selective beta-difluorination with Selectfluor (R). Compounds 1f and 2c were selected for in vivo assessment and demonstrated selective lowering of A beta 42 in a genetically engineered mouse model of APP processing. Moreover, in a 7-day safety study, rats treated orally with compound 1f (250 mg/kg per day, AUC(0-24) = 2100 mu M h) did not exhibit Notch-related effects. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.034

文献信息

• DIFLUORINATED PIPERIDINES FOR TREATMENT OF ALZHEIMER'S DISEASE AND RELATED CONDITIONS
  申请人：Stanton Matthew G.

  公开号：US20100010041A1

  公开（公告）日：2010-01-14

  Compounds of formula (I). Selectively inhibit production of Aβ(1-42) and hence find use in treatment of diseases associated with deposition of β-amyloid in the brain.

  公式为(I)的化合物，能够选择性地抑制Aβ(1-42)的产生，因此可用于治疗与β-淀粉样蛋白在大脑中沉积相关的疾病。
• WO2008/30391
  申请人：——

  公开号：——

  公开（公告）日：——
• Fluorinated piperidine acetic acids as γ-secretase modulators
  作者：Matthew G. Stanton、Jed Hubbs、David Sloman、Christopher Hamblett、Paula Andrade、Minilik Angagaw、Grace Bi、Regina M. Black、Jamie Crispino、Jonathan C. Cruz、Eric Fan、Georgia Farris、Bethany L. Hughes、Candia M. Kenific、Richard E. Middleton、George Nikov、Peter Sajonz、Sanjiv Shah、Nirah Shomer、Alexander A. Szewczak、Flobert Tanga、Matthew T. Tudge、Mark Shearman、Benito Munoz

  DOI：10.1016/j.bmcl.2009.11.034

  日期：2010.1

  We report herein a novel series of difluoropiperidine acetic acids as modulators of gamma-secretase. Synthesis of 2-aryl-3,3-difluoropiperidine analogs was facilitated by a unique and selective beta-difluorination with Selectfluor (R). Compounds 1f and 2c were selected for in vivo assessment and demonstrated selective lowering of A beta 42 in a genetically engineered mouse model of APP processing. Moreover, in a 7-day safety study, rats treated orally with compound 1f (250 mg/kg per day, AUC(0-24) = 2100 mu M h) did not exhibit Notch-related effects. (C) 2009 Elsevier Ltd. All rights reserved.